Mesothelin Immunotherapy for Cancer: Ready for Prime Time?

被引：249
作者：
Hassan, Raffit [1 ]
Thomas, Anish [1 ]
Alewine, Christine [1 ]
Le, Dung T. [2 ]
Jaffee, Elizabeth M. [2 ]
Pastan, Ira [1 ]
机构：
[1] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA
来源：
JOURNAL OF CLINICAL ONCOLOGY | 2016年 / 34卷 / 34期
基金：
美国国家卫生研究院;
关键词：
PANCREATIC DUCTAL ADENOCARCINOMA; PROLONGED PATIENT SURVIVAL; TRIPLE-NEGATIVE BREAST; MONOCLONAL-ANTIBODY K1; EXTRAHEPATIC BILE-DUCT; PHASE-I TRIAL; OVARIAN-CANCER; RECOMBINANT IMMUNOTOXIN; EXPRESSING MESOTHELIN; PLEURAL MESOTHELIOMA;
D O I：
10.1200/JCO.2016.68.3672
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer. (C) 2016 by American Society of Clinical Oncology
引用
收藏
页码：4171 / +
页数：10
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